Signal pathways mediating oxytocin stimulation of prostaglandin synthesis in select target cells

A major action of oxytocin is to stimulate prostaglandin production in repr oductive tissues. The two major enzyme systems involved are cytosolic phosp holipase A(2) (cPLA(2)), which catalyses the formation of arachidonic acid from membrane glycerophospholipids, and prostaglandin endoperoxide-H syntha ses-1 and -2, which allow conversion of arachidonic acid to prostaglandins. During gestation, the concentrations of all three enzymes rise in the rabb it amnion. Agonists, including oxytocin, increase cPLA(2) activity, in part , by elevating intracellular Ca2+ concentration, which causes cPLA(2) to be translocated from the cytosol to intracellular membrane binding sites. Cyt osolic PLA(2) is then activated by a mitogen-activated protein kinase (MAPK )-dependent step. Our studies have elucidated signal pathways involved in o xytocin-stimulated prostaglandin output in both rabbit amnion cells and Chi nese hamster ovary cells stably transfected with the rat oxytocin receptor. The two cell types are alike with respect to oxytocin-stimulated intracell ular Ca2+ transients, mediation via G(q), and the specific MAPK that cataly ses the phosphorylation of cPLA(2). However, they differ with respect to th e mechanisms of upregulation of key enzymes involved in prostaglandin E-2 s ynthesis. These findings illustrate the tiers of complementary mechanisms i nvolved in oxytocin stimulation of prostaglandin E-2, and the extent of the diversity in the cellular signalling pathways involved.